This project will examine the immunologic mechanisms operative in vivo during eradication of disseminated leukemia by specific immunotherapy and will study methods to manipulate the immune system so as to promote tumor destruction. Most studies will be performed in an adoptive chemoimmunmotherapy model in which mice can be cured of disseminated leukemia by combined treatment with nonlethal noncurative chemotherapy and adoptively transferred specifically immune syngeneic t lymphocytes. The potential in vivo effector mechanisms and the role of host and donor cells will be analyzed by utilizing techniques for isolating and purifying functional subpopulations of immune donor cells for use in adoptive transfer, and by producing leukemic hosts which are either T-deficient or have selective immunodeficiencies. Manipulation of the immune system in vivo will be studied by inoculation of monoclonal antibodies which recognize T cell determinants. With the use of donor and host mice congenic for genes encoding for T cell antigens and antibodies of appropriate specificity, host and/or donor subpopulations will be selectively depleted in vivo at different time points before or after therapy, and the effect of tumor eradication determined. These studies should define the immunologic mechanisms operative in vivo which promote, inhibit, or mediate tumor destruction, and determine how tumor immunity can be modulated to facilitate tumor destruction by both adoptive transfer of functional subsets of syngeneic lymphocytes and inoculation of antibodies to T cell subpopulations. The methods developed and principles elucidated in these adoptive immunotherapy models utilizing syngeneic lymphocytes obtained from immunized non-tumor-bearing mice will be extrapolated to determine if an animal with disseminated progressive leukemia can serve as a source of lymphocytes which, after appropriate purification and amplification in vitro and/or modulation in vivo, can eliminate the disseminated disease.